Treatment of Deep Vein Thrombosis

Deep vein thrombosis is treated with anticoagulation to stop clot extension, prevent pulmonary embolism and reduce recurrence. Treatment starts as soon as the diagnosis is likely, before imaging if imaging is delayed and there is no bleeding risk, and is continued for a duration set by whether the clot was provoked, unprovoked or cancer-related.

Diagnosis first. Use a pre-test score (such as Wells) with a D-dimer and compression ultrasound. Start treatment while waiting if the probability is high.

Treatment phases. Initial phase (first 5 to 21 days), treatment phase (to 3 months) and extended phase (beyond 3 months, for selected patients).

First choice for most patients is a direct oral anticoagulant:

• Apixaban 10 mg orally twice daily for 7 days, then 5 mg twice daily.
• Rivaroxaban 15 mg orally twice daily with food for 21 days, then 20 mg once daily with food.
• Dabigatran 150 mg orally twice daily after at least 5 days of parenteral anticoagulation.
• Edoxaban 60 mg orally once daily after at least 5 days of parenteral anticoagulation; 30 mg once daily if creatinine clearance is 15 to 50 mL/min, weight is 60 kg or less, or a strong P-glycoprotein inhibitor is used.

Parenteral or vitamin K antagonist options:

• Enoxaparin 1 mg/kg subcutaneously twice daily, or 1.5 mg/kg once daily, for at least 5 days.
• Dalteparin 200 units/kg once daily (maximum 18,000 units) for the first month in cancer.
• Fondaparinux 7.5 mg once daily (5 mg if under 50 kg, 10 mg if over 100 kg).
• Unfractionated heparin: bolus 80 units/kg intravenously then 18 units/kg/h, adjusted to aPTT 1.5 to 2.5 times control or anti-Xa 0.3 to 0.7 units/mL.
• Warfarin: start with parenteral anticoagulation and overlap for at least 5 days and until INR is 2.0 or more for 24 hours. Target INR 2.0 to 3.0.

Duration. Provoked by a major transient factor (surgery): 3 months. Unprovoked or minor transient factor: at least 3 months, then consider extended treatment. Extended therapy: apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily after 6 months of full-dose treatment. Distal calf clot with symptoms: 3 months, or serial imaging.

Kidney impairment. Creatinine clearance 15 to 30 mL/min: enoxaparin 1 mg/kg once daily, or unfractionated heparin; avoid dabigatran under 30 mL/min and avoid rivaroxaban, apixaban and edoxaban under 15 mL/min.

Liver impairment. Avoid direct oral anticoagulants in moderate to severe liver disease (Child-Pugh B and C); low molecular weight heparin is used with care.

Obesity. Usual dose apixaban and rivaroxaban are acceptable to 120 kg or body mass index 40.

Interactions. Avoid apixaban, rivaroxaban and edoxaban with rifampicin, carbamazepine, phenytoin and ritonavir-boosted antiretrovirals.

Special groups. Pregnancy needs low molecular weight heparin. In East Africa, warfarin and low molecular weight heparin are the most available agents, direct oral anticoagulants are costly, and tuberculosis treatment with rifampicin makes warfarin dosing unstable.

Monitoring. Check full blood count, creatinine and liver tests at baseline and at least yearly, and every 3 months in older adults and those with kidney impairment. Check INR twice weekly in the first week on warfarin, then weekly.

Referral and escalation. Refer for phlegmasia (catheter-directed thrombolysis), iliofemoral clot with severe symptoms, recurrence on treatment, bleeding, and absolute contraindication to anticoagulation (consider an inferior vena cava filter).

Stopping. Review the benefit and bleeding risk at 3 months and then yearly. Stop anticoagulation at 3 months after a major transient provoker.